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Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis
Jin, Yujuan1,2,3; Zhao, Qiqi1,2,3; Zhu, Weikang4; Feng, Yan1,2,3; Xiao, Tian5; Zhang, Peng6; Jiang, Liyan7; Hou, Yingyong8; Guo, Chenchen1,2,3; Huang, Hsinyi1,2,3; Chen, Yabin1,2,3; Tong, Xinyuan1,2,3; Cao, Jiayu1,2,3; Li, Fei1,9; Zhu, Xueliang2,3,10; Qin, Jun11; Gao, Dong1,2,3; Liu, Xin-Yuan1,2,3; Zhang, Hua12; Chen, Luonan1,2,3,14; Thomas, Roman K.13,15; Wong, Kwok-Kin12; Zhang, Lei1,2,3,14; Wang, Yong4,14; Hu, Liang1,2,3; Ji, Hongbin1,2,3,14
2022-07-01
Source PublicationNATIONAL SCIENCE REVIEW
ISSN2095-5138
Volume9Issue:7Pages:15
AbstractSmall-cell lung cancer (SCLC) is a recalcitrant cancer characterized by high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using a Rb1(L/L)/Trp53(L/L) mouse model, we identify the NCAM(hi)CD44(lo/-) subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAM(lo)CD44(hi) cell (non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal the important role of the SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by the SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as the key molecular switch in orchestrating SCLC phenotypic transition and metastasis.
Keywordsmall cell lung cancer SWI SNF complex TAZ phenotypic transition metastasis
DOI10.1093/nsr/nwab232
Indexed BySCI
Language英语
Funding ProjectNational Natural Science Foundation of China[81871875] ; National Natural Science Foundation of China[82173340] ; National Natural Science Foundation of China[82030083] ; National Natural Science Foundation of China[81872312] ; National Natural Science Foundation of China[82011540007] ; National Natural Science Foundation of China[31621003] ; National Natural Science Foundation of China[81402371] ; National Natural Science Foundation of China[12025107] ; National Basic Research Program of China[2017YFA0505501] ; National Basic Research Program of China[2020YFA0803300] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19020201] ; Basic Frontier Scientific Research Program of the Chinese Academy of Sciences[ZDBSLY-SM006] ; International Cooperation Project of the Chinese Academy of Sciences[153D31KYSB20190035] ; Innovative Research Team of High-Level Local Universities in Shanghai[SSMU-ZLCX20180500] ; Science and Technology Commission of Shanghai Municipality[21ZR1470300]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000883232400001
PublisherOXFORD UNIV PRESS
Citation statistics
Document Type期刊论文
Identifierhttp://ir.amss.ac.cn/handle/2S8OKBNM/60699
Collection应用数学研究所
Corresponding AuthorWang, Yong; Hu, Liang; Ji, Hongbin
Affiliation1.Chinese Acad Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
3.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China
4.Chinese Acad Sci, Key Lab Management Decis & Informat Syst, Natl Ctr Math & Interdisciplinary Sci,Acad Math &, Ctr Excellence Math Sci,Hua Loo Keng Ctr Math Sci, Beijing 100190, Peoples R China
5.Shenzhen Univ, Shenzhen Key Lab Translat Med Tumor, Dept Cell Biol & Genet, Hlth Sci Ctr, Shenzhen 518060, Peoples R China
6.Tongji Univ, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
7.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai 200030, Peoples R China
8.Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China
9.Fudan Univ, Dept Pathol, Sch Basic Med Sci, Shanghai 200032, Peoples R China
10.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China
11.Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth Sci, Shanghai 200031, Peoples R China
12.New York Univ, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA
13.Univ Cologne, Dept Translat Gen, Ctr Integrated Oncol, D-50931 Cologne, Germany
14.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
15.Univ Hosp Cologne, Dept Pathol, D-50937 Cologne, Germany
Recommended Citation
GB/T 7714
Jin, Yujuan,Zhao, Qiqi,Zhu, Weikang,et al. Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis[J]. NATIONAL SCIENCE REVIEW,2022,9(7):15.
APA Jin, Yujuan.,Zhao, Qiqi.,Zhu, Weikang.,Feng, Yan.,Xiao, Tian.,...&Ji, Hongbin.(2022).Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis.NATIONAL SCIENCE REVIEW,9(7),15.
MLA Jin, Yujuan,et al."Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis".NATIONAL SCIENCE REVIEW 9.7(2022):15.
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